Pulmonary ventilation using high frequencies (1.0 to 30 Hz) and small tidal volumes (less than anatomic dead space) is a relatively recent method of mechanical ventilation which has potential advantages over conventional ventilatory techniques due to the presumed lower alveolar-pressures generated by the small tidal volumes. This technique has been successfully applied in a number of clinical situations including ventilation of patients during anesthesia and patients with bronchopleural fistulae. However, the widespread application of high frequency ventilation (HFV) in the clinical setting has been partially hampered by a lack of knowledge of the physical mechanisms enhancing gas exchange by this technique. It is our hypothesis that insight into the physical mechanisms that produce gas exchange during HFV can be obtained by analyzing the gas concentration gradients thought to exist in the lung during HFV, which act as markers of the underlying physical processes. By using new analytic techniques which we have developed, data obtained by measuring single breath nitrogen washout (SBNW) curves or single breath CO2 washout curves following HFV will yield information concerning the effectiveness of gas mixing at many points in the lung. The concentration gradients developed in the lung during HFV represent the complex interaction of mechanisms related to various fields including physiology, fluid mechanics and mass transfer. Thus, we propose a multidisciplinary approach in which we will concurrently study (1) dogs and humans (2) networks of branching tubes with lung-like geometry and (3) theoretical models of gas mixing. The specific techniques developed (e.g., SBNW curves) may prove useful in rationally determining the most appropriate method of applying HFV clinically to specific patients while the results of these studies should help in furthering our understanding of the mechanisms by which HFV promotes gas exchange in humans.